Pharmaceutical agents provide diagnostic and therapeutic utility that are central to patient care. However, all agents also carry adverse drug effect profiles. While most of these are clinically insignificant, some drugs may cause unacceptable toxicity that impacts negatively on patient morbidity and mortality. Recognizing adverse effects is important for administering appropriate drug doses, instituting preventive strategies, and withdrawing the offending agent due to toxicity. In the present article, we will review those drugs that are associated with impaired renal function. By focusing on pharmaceutical agents that are currently in clinical practice, we will provide an overview of nephrotoxic drugs that a treating physician is most likely to encounter. In doing so, we will summarize risk factors for nephrotoxicity, describe clinical manifestations, and address preventive and treatment strategies.
Mycobacterium neoaurum is a rare cause of bacteremia, and infection usually occurs in an immunocompromised host in the setting of an indwelling catheter. Prosthetic valve endocarditis due to non-tuberculous mycobacteria typically carries a dismal prognosis; we report a case of M. neoaurum prosthetic valve endocarditis with favorable response to antimicrobial therapy without surgical intervention.
A 27-year-old woman with osteosarcoma involving the left distal femur was treated with high-dose methotrexate (5.5 g/m 2 Â1 dose). One liter of isotonic sodium bicarbonate solution was infused and maintained to achieve a urine pH greater than 7.1. Within 48 h, serum creatinine rapidly rose from 0.9 to 1.6 mg/dl, consistent with acute kidney injury (AKI), despite urine output 4100 ml/h. Methotrexate level was 49 mm/l. Urinalysis: SG 1.010, pH 8.5, and glucose, protein, and leukocyte esterase were negative. Urine microscopy revealed numerous brownish/gold crystals, which were in clumps ( Figure 1a) and casts (Figure 1b)-consistent with methotrexate crystalline nephropathy. Five days later, kidney function returned to baseline.High-dose methotrexate causes AKI through multiple possible mechanisms including direct tubular toxicity associated with decreased adenosine deaminase activity and intratubular crystal precipitation. 1 Methotrexate and its metabolites, which are poorly soluble in an acid pH, precipitate within the renal tubular lumens in the setting of an acidic urine, decreased urinary flow rates, and when high urinary concentrations are present. 1 Crystal precipitation results in both distal renal tubular obstruction and associated tubulointerstitial inflammation. 1,2 Methotrexate-associated AKI develops in approximately 2% of patients, is typically non-oliguric, and is generally reversible. 1 AKI prevention hinges on induction of high urinary flow rates and an alkaline urine pH (47.1) by reducing precipitation of crystals within tubular lumens. When AKI develops, highflux hemodialysis and carboxypeptidase-G2 are utilized to lower plasma levels. However, hemodialysis is inefficient and associated with post-dialysis rebound. Carboxypeptidase-G2 effectively lowers methotrexate levels via metabolism to nontoxic metabolites but is extremely costly. 1 Our case is unusual in that AKI and significant methotrexate crystalluria developed despite adequate urinary alkalinization and urine flow rates. In addition, methotrexate Figure 1 | Methotrexate crystals are seen in clumps (a) and in a cast (b).
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